Pulmonary infection is a common occurrence in immunocompromised patients and is associated with high mortality. Immunosuppressing drugs, such as glucocorticosteroids and cyclophosphamide, have been associated with specific defects in systemic immune function but little is known regarding their effects on local pulmonary host defense mechanisms. This project will evaluate drug-induced pulmonary immunopathology in an animal model of immunosuppression and based upon this information, attempts will be made to enhance pulmonary host defense during periods of peak susceptibility. Guinea pigs will receive one week courses of parenteral cortisone acetate, 100 mg/Kg/day plus cyclophosphamide, 15 mg/Kg/day or 30 mg/Kg/day. Bronchoalveolar lavage fluids will then be obtained for cell enumeration, differentiation and studies of the functional capabilities of cells (alveolar macrophages and lymphocytes) during immunosuppressed states. Normal animals will serve as controls. Besides cell numbers, an evaluation of antibacterial functions, phagocyte chemotaxis, complement synthesis by macrophages, and lymphocyte-lymphokine production will be made. In addition, the effects of immunosuppressing drugs on the kinetics of pulmonary inflammation will be determined. Serial tissue sections will be obtained from normal and immunosuppressed animals after intratracheal bacterial challenge (Pseudomonas aeruginosa). Descriptive and quantitative histopathologic observations will provide insight into differences in rates of accumulation of inflammatory cells in lung tissue. Finally, attempts to bolster defective lung host defense during immunosuppression will include granulocyte transfusions and use of a lipopolysaccharide pseudomonas vaccine.